Research Proposal: Pathogens within the genus Anaplasma (order Rickettsiales) cause human and animal diseases including human granulocytic ehrlichiosis (HGE), equine ehrlichiosis, and bovine and ovine anaplasmosis. These pathogens are small, Gram-negative, obligately intracellular bacteria that require ixodid ticks for transmission. Infection within the tick is initiated during a blood meal on an infected mammal. Anaplasma then enters the midgut epithelial cells, replicates, and moves to the salivary glands. The bacteria are transmitted via the salivary secretion when the infected tick ingests a second blood meal. Importantly, differences in the tick transmissibility of both A. phagocytophila and A. marginale have been identified. There is strong correlation between the incidence of HGE and the amount of genetic variation in the bacterial population suggesting that only certain A. phagocytophila genotypes are transmitted from the reservoir species to humans. However, the genetic determinants of pathogen transmissibility by ticks are unknown, representing a significant gap in our knowledge relevant to prevention of disease outbreaks. I propose to study transmissible and non-transmissible strains of Anaplasma marginale as a model to identify the molecular determinants of Anaplasma spp. transmission. The Candidate: The candidate is a veterinarian with two years of experience in clinical practice, including an internship, and will complete her 3 year residency in anatomic pathology in June 2002. In preparation for research raining, the candidate has completed the didactic course work for the PhD and passed the doctoral preliminary examination. The research proposed in this document constitutes her plan to complete doctoral research focusing on vector borne and emergent disease. Environment: The Department of Veterinary Microbiology and Pathology provides both modern research facilities for infectious disease research and a highly interactive training environment including intra- and interdisciplinary graduate education and extensive collaboration both within and the outside the university. The sponsor has an active research program in vector borne disease has successfully mentored clinicians, graduate students, and post-doctoral fellows to research independence.